Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users

Abstract

Importance: Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve drug response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking genotype to drug response phenotypes; however, it is unclear which pharmacogenetic tests, if implemented, would provide the greatest utility for a given patient population.

Objectives: To project the proportion of veterans in the US Veterans Health Administration (VHA) with actionable pharmacogenetic variants and evaluate how testing might be associated with prescribing decisions.

Design, setting, and participants: This cross-sectional study included veterans who used national VHA pharmacy services from October 1, 2011, to September 30, 2017. Data analyses began April 26, 2018, and were completed February 6, 2019.

Exposures: Receipt of level A drugs based on VHA pharmacy dispensing records.

Main outcomes and measures: Projected prevalence of actionable pharmacogenetic variants among VHA pharmacy users based on variant frequencies from the 1000 Genomes Project and veteran demographic characteristics; incident number of level A prescriptions, and proportion of new level A drug recipients projected to carry an actionable pharmacogenetic variant.

Results: During the study, 7 769 359 veterans (mean [SD] age, 58.1 [17.8] years; 7 021 504 [90.4%] men) used VHA pharmacy services. It was projected that 99% of VHA pharmacy users would carry at least 1 actionable pharmacogenetic variant. Among VHA pharmacy users, 4 259 153 (54.8%) received at least 1 level A drug with 1 188 124 (15.3%) receiving 2 drugs, and 912 189 (11.7%) receiving 3 or more drugs. The most common incident prescriptions during the study were tramadol (923 671 new recipients), simvastatin (533 928 new recipients), citalopram (266 952 new recipients), and warfarin (205 177 new recipients). Gene-drug interactions projected to have substantial clinical impacts in the VHA population include the interaction of SLCO1B1 with simvastatin (1 988 956 veterans [25.6%]), CYP2D6 with tramadol (318 544 veterans [4.1%]), and CYP2C9 or VKORC1 with warfarin (7 163 349 veterans [92.2%]).

Conclusions and relevance: Clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants. These results suggest that pharmacogenetic testing has the potential to affect pharmacotherapy decisions for commonly prescribed outpatient medications for many veterans.

Conflict of interest statement

Conflict of Interest Disclosures: Dr DuVall reported grants, personal fees, and nonfinancial support from the US Department of Veterans Affairs during the conduct of the study and grants from AbbVie, Amgen, Anolinx, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Genentech, Genomic Health, Gilead Sciences, GlaxoSmithKline, Innocrin Pharmaceuticals, Janssen Pharmaceuticals, Kantar Health, Myriad Genetics, Novartis, and PAREXEL International outside the submitted work. Dr Voight reported serving as a statistical reviewer and receiving personal fees from JAMA Network Open outside the submitted work. Dr Oslin reported grants from the Department of Veteran Affairs during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Use of Level A Drugs and Combinations Among Veterans Health Administration Pharmacy Users from October 1, 2011, to September 30, 2017

A, Proportion of Veterans Health Administration pharmacy users prescribed 1 or more level A drugs. B, Proportion of Veterans Health Administration pharmacy users newly prescribed 1 or more level A drugs. C, Proportion of new drug recipients receiving the most common combinations of level A drugs by drug classes.

Figure 2.. Projected Numbers of New Drug Recipients With Actionable and Nonactionable Phenotypes for the Top 10 Level A Drugs

Projections based on the numbers of Veterans Health Administration pharmacy users receiving a new prescription for each drug from October 1, 2011, to September 30, 2017. Numbers are presented for all patients receiving clopidogrel and for patients receiving clopidogrel after a percutaneous coronary intervention (PCI) because of the larger clinical impact of the pharmacogenetic variant for this indication.

Figure 3.. Projected Veterans Health Administration (VHA) Population Exposed to a Drug With High Risk of Toxic Effects or Nonefficacy from October 1, 2011, to September 30, 2017

Medications with a strong level A recommendation to either avoid or adjust the dose based on available pharmacogenetic test results are included. The x-axis depicts the increasing risk of toxic effects or adverse drug reaction in response to drug exposure for patients with select phenotypes. The y-axis depicts the spectrum of anticipated efficacy of the drug for patients with select phenotypes—those with certain phenotypes are at higher risk of drug nonresponse. The number of patients projected to be carriers of the genetic variant or specific phenotype is based on the numbers of new drug recipients from October 1, 2011, to September 30, 2017.